5-methoxy-3-bromomethyl-benzothiophene | 40862-92-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 5-methoxy-3-bromomethyl-benzothiophene
• 英文别名: 3-(Bromomethyl)-5-methoxy-1-benzothiophene
• CAS: 40862-92-8
• 化学式: C₁₀H₉BrOS
• 分子量: 257.151
• InChiKey: XEFXOWYMNJFHKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  37.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methoxy-3-bromomethyl-benzothiophene 在 乌洛托品 、 potassium hydroxide 作用下， 以 乙醇 、 氯仿 、 水 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Development of a Novel Class of Tubulin Inhibitor from Desmosdumotin B with a Hydroxylated Bicyclic B-Ring

  摘要：

  A series of newly synthesized hydroxylated analogues of triethyldesmosdumotin B (TEDB) with a bicyclic B-ring exhibited a significantly different mode of action for affecting microtubule dynamics and spindle formation but had the same antiproliferative activity spectrum, including activity against multidrug-resistant tumors. These analogues efficiently induced cell cycle arrest at prometaphase and caused formation of immature multipolar spindles. 6'-Hydroxyl TEDB-TB (8) disrupted bipolar spindle formation but had a negligible effect on interphase microtubules. On the basis of the predicted binding modes of the new compounds with tubulin dimer, compound 4 forms three hydrogen bonds (H-bonds) only with alpha-tubulin at the colchicine site; in contrast, 8 forms H-bonds with both alpha- and beta-tubulin. We predict that, when a compound/ligand, such as 8, forms H-bonds to both alpha- and beta-tubulins, spindle formation is disrupted more than the dynamics of interphase microtubules. This result may reflect the well-known greater dynamicity of spindle microtubules as compared with interphase microtubules.

  DOI：

  10.1021/jm501859j
• 作为产物：
  描述：

  1-[(4-甲氧基苯基)硫基]丙酮 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 甲苯 为溶剂， 反应 19.5h， 生成 5-methoxy-3-bromomethyl-benzothiophene
  参考文献：
  名称：

  Development of a Novel Class of Tubulin Inhibitor from Desmosdumotin B with a Hydroxylated Bicyclic B-Ring

  摘要：

  A series of newly synthesized hydroxylated analogues of triethyldesmosdumotin B (TEDB) with a bicyclic B-ring exhibited a significantly different mode of action for affecting microtubule dynamics and spindle formation but had the same antiproliferative activity spectrum, including activity against multidrug-resistant tumors. These analogues efficiently induced cell cycle arrest at prometaphase and caused formation of immature multipolar spindles. 6'-Hydroxyl TEDB-TB (8) disrupted bipolar spindle formation but had a negligible effect on interphase microtubules. On the basis of the predicted binding modes of the new compounds with tubulin dimer, compound 4 forms three hydrogen bonds (H-bonds) only with alpha-tubulin at the colchicine site; in contrast, 8 forms H-bonds with both alpha- and beta-tubulin. We predict that, when a compound/ligand, such as 8, forms H-bonds to both alpha- and beta-tubulins, spindle formation is disrupted more than the dynamics of interphase microtubules. This result may reflect the well-known greater dynamicity of spindle microtubules as compared with interphase microtubules.

  DOI：

  10.1021/jm501859j

文献信息

• Aminoguanidines
  申请人：SANDOZ LTD.

  公开号：EP0505322A1

  公开（公告）日：1992-09-23

  Compounds of formula         A-X--Y-NH-B wherein A is derived from optionally substituted benzothiophene, indole, 4-aza-and 7-aza-benzothiophene or-indole, A bearing in position 5 hydrogen, halogen, optionally substituted alkyl, hydroxy, nitro, amino, alkylamino, acylamino, alcoxycarbonyl, sulfamoyl, cyano, trimethylsilyl, carboxy, carbamoyl, phosphate, oxycarbamoyl, heterocyclic radical or ether or ester group, X---Y is -CR₈=N- or CH(R₈)-NH- wherein R₈ is -H or alkyl and attached at position 3 of A, and B is a heterocyclic radical or a residue wherein R₁₀ is H, optionally substituted alkyl, cycloalkyl, aryl, adamantyl, acyl or carbamoyl and X₂ is alkylthio or NR₃R₁₀ wherein R₃ is H or alkyl or R₃ and R₁₀ together with the nitrogen atom to which they are attached form a heterocyclic radical, in free form or in salt form, have pharmacological activity, e.g. for treating gastrointestinal disorders.

  式的化合物 A-X--Y-NH-B 其中 A 来自任选取代的苯并噻吩、吲哚、4-氮杂和 7-氮杂苯并噻吩或吲哚，A 在第 5 位含有氢、卤素、任选取代的烷基、羟基、硝基、氨基、烷基氨基、酰氨基、烷氧基羰基、氨基磺酰基、氰基、三甲基硅基、羧基、氨基甲酰基、磷酸基、氧氨基甲酰基、杂环基或醚或酯基、氰基、三甲基硅基、羧基、氨基甲酰基、磷酸基、氧氨基甲酰基、杂环基、醚基或酯基，X--Y 是-CR₈=N- 或 CH(R₈)-NH- 其中 R₈ 是-H 或烷基并连接在 A 的第 3 位，B 是杂环基或残基。 其中 R₁₀ 是 H、任选取代的烷基、环烷基、芳基、金刚烷基、酰基或氨基甲酰基、X₂是烷硫基或 NR₃R₁₀，其中 R₃ 是 H 或烷基，或 R₃ 和 R₁₀ 与它们连接的氮原子一起形成杂环基。例如，用于治疗胃肠道疾病。
• US5510353A
  申请人：——

  公开号：US5510353A

  公开（公告）日：1996-04-23
• Development of a Novel Class of Tubulin Inhibitor from Desmosdumotin B with a Hydroxylated Bicyclic B-Ring
  作者：Kyoko Nakagawa-Goto、Akifumi Oda、Ernest Hamel、Emika Ohkoshi、Kuo-Hsiung Lee、Masuo Goto

  DOI：10.1021/jm501859j

  日期：2015.3.12

  A series of newly synthesized hydroxylated analogues of triethyldesmosdumotin B (TEDB) with a bicyclic B-ring exhibited a significantly different mode of action for affecting microtubule dynamics and spindle formation but had the same antiproliferative activity spectrum, including activity against multidrug-resistant tumors. These analogues efficiently induced cell cycle arrest at prometaphase and caused formation of immature multipolar spindles. 6'-Hydroxyl TEDB-TB (8) disrupted bipolar spindle formation but had a negligible effect on interphase microtubules. On the basis of the predicted binding modes of the new compounds with tubulin dimer, compound 4 forms three hydrogen bonds (H-bonds) only with alpha-tubulin at the colchicine site; in contrast, 8 forms H-bonds with both alpha- and beta-tubulin. We predict that, when a compound/ligand, such as 8, forms H-bonds to both alpha- and beta-tubulins, spindle formation is disrupted more than the dynamics of interphase microtubules. This result may reflect the well-known greater dynamicity of spindle microtubules as compared with interphase microtubules.